The goal of the research proposed in this application is to test the hypothesis that antibacterial agents can be attached covalently to chemically-reactive groups of the tooth-associated, proteinaceous pellicle and that these bound-agents will inhibit bacterial colonization of treated tooth surfaces. It is proposed that this hypothesis be tested in three phases. 1. Examination of the tooth-associated, acquired pellicle for covalent binding sites is the first phase of the proposed work. The experimental approach in this phase depends on covalently attaching detectable agents such as radioactive glycyl ethyl ester, dansyl chloride, fluorescein isothiocyanate, or radioactive diisopropylfluorophosphate to appropriate amino-acid, side-chain groups of the tooth-borne pellicle. 2. Coupling of antibacterial agents to the tooth-associated pellicle by covalent interaction is the second phase of the proposed research. The experimental approach for this phase depends on the information generated during the initial phase of the proposed research. For example, sulfonamides with appropriate reactive groups (e.g. sulfadiazine sodium) will be tested for covalent coupling to available carboxyl groups of the tooth-associated pellicle. 3. Evaluation of the effectiveness of covalently-attached, antibacterial agents to inhibit or prevent bacterial colonization of treated tooth surfaces is the third phase of the proposed research. The comparison of in vitro, bacterial colonization of treated and untreated extracted, human teeth will be achieved by visual examination where that is appropriate or by chemical (e.g., comparison of bacterial DNA from treated and untreated pellicles) analysis where that is appropriate.